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New biosensors bring industrial biomanufacturing one step closer

“Accelerating evolution to make awesome amounts of valuable chemicals.” This is how Wyss Institute core faculty member George Church described his group’s ongoing biomanufacturing research at Harvard’s Wyss Institute for Biologically Inspired Engineering. These researchers envision a future in which “fleets of genetically engineered bacterial cells, such as common E. coli” have been reprogrammed to create valuable chemical commodities in an environmentally friendly way.

“Accelerating evolution to make awesome amounts of valuable chemicals.” This is how Wyss Institute core faculty member George Church described his group’s ongoing biomanufacturing research at Harvard’s Wyss Institute for Biologically Inspired Engineering. These researchers envision a future in which “fleets of genetically engineered bacterial cells, such as common E. coli” have been reprogrammed to create valuable chemical commodities in an environmentally friendly way. By leveraging their natural metabolic processes, bacteria could be reprogrammed to convert readily available sources of natural energy into pharmaceuticals, plastics and fuel products.

Now, in a recent article published in the Nucleic Acids Research journal, Wyss Institute researchers led by Church Critical report that they have taken a new step towards realizing this vision. As they explain, critical to this process of metabolically engineering microbes is the use of biosensors. Biosensors act as the switches and levers that turn programmed functions on and off inside the engineered cells. They also can be used to detect which microbial “workers” are producing the most voluminous amounts of a desired chemical.

The problem was that the biosensors available up until now had little relevance to the biomanufacturing of valuable chemicals. Wyss Institute researchers led by Church have successfully developed a new suite of such sensors, which not only increase the number of cellular “switches and levers” that scientists can use for complex genetic reprogramming, but also respond to valuable products such as renewable plastics or costly pharmaceuticals. The sensors also give microbes a “voice” to report on their own efficiency in making these products, which allows the scientists to communicate with cells much more effectively, and vice versa.

The team at Harvard’s Wyss Institute for Biologically Inspired Engineering aims to leverage the new biosensors to aid in its efforts to develop renewable chemical production strategies using genetically engineered microbes.

Linked to green fluorescent protein, the biosensors can be used to trigger individual cells to give off visible fluorescence in a rate directly proportional to how well they are able to produce a desired chemical commodity. Using the new biosensors, the most efficient microbial workers are easily identified so that they can serve as the predecessors for colonies of engineered bacteria that evolve to become more efficient at producing renewable chemicals with each subsequent generation. This drastically reduces the bottleneck of the design-build-test cycle, which historically has been caused by engineers having to sift through teeming bacteria colonies to find top producers.

The findings could also lead to new applications in environmental monitoring using genetically engineered microbes to issue warning signals in the presence of pollutants or toxins, and could unlock new fundamental insights into metabolic pathways.

 

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